TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9331	28216;28217;28218	chr2:178711245;178711244;178711243	chr2:179575972;179575971;179575970
N2AB	9014	27265;27266;27267	chr2:178711245;178711244;178711243	chr2:179575972;179575971;179575970
N2A	8087	24484;24485;24486	chr2:178711245;178711244;178711243	chr2:179575972;179575971;179575970
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-79
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.5311
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
S/A	None	None	0.019	None	0.179	0.1	0.1749357433	gnomAD-4.0.0	1.36836E-06	None	None	None	None	I	None	2.98757E-05	0	None	0	0	None	0	0	8.99457E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
S/A	0.0724	likely_benign	0.0775	benign	-0.665	Destabilizing	0.019	N	0.179	neutral	None	None	None	None	I
S/C	0.159	likely_benign	0.1733	benign	-0.499	Destabilizing	0.946	D	0.454	neutral	None	None	None	None	I
S/D	0.171	likely_benign	0.2298	benign	0.386	Stabilizing	0.055	N	0.231	neutral	None	None	None	None	I
S/E	0.1744	likely_benign	0.2443	benign	0.36	Stabilizing	None	N	0.097	neutral	None	None	None	None	I
S/F	0.1352	likely_benign	0.1418	benign	-1.171	Destabilizing	0.602	D	0.513	neutral	None	None	None	None	I
S/G	0.0973	likely_benign	0.1143	benign	-0.839	Destabilizing	0.104	N	0.241	neutral	None	None	None	None	I
S/H	0.1555	likely_benign	0.1846	benign	-1.196	Destabilizing	0.497	N	0.475	neutral	None	None	None	None	I
S/I	0.1003	likely_benign	0.1168	benign	-0.319	Destabilizing	0.124	N	0.411	neutral	None	None	None	None	I
S/K	0.243	likely_benign	0.3405	ambiguous	-0.341	Destabilizing	0.055	N	0.245	neutral	None	None	None	None	I
S/L	0.0891	likely_benign	0.0875	benign	-0.319	Destabilizing	0.055	N	0.328	neutral	None	None	None	None	I
S/M	0.1432	likely_benign	0.1446	benign	-0.264	Destabilizing	0.667	D	0.474	neutral	None	None	None	None	I
S/N	0.0855	likely_benign	0.1027	benign	-0.334	Destabilizing	0.104	N	0.242	neutral	None	None	None	None	I
S/P	0.65	likely_pathogenic	0.7308	pathogenic	-0.404	Destabilizing	0.301	N	0.421	neutral	None	None	None	None	I
S/Q	0.2039	likely_benign	0.2589	benign	-0.415	Destabilizing	0.001	N	0.127	neutral	None	None	None	None	I
S/R	0.2013	likely_benign	0.2764	benign	-0.253	Destabilizing	0.124	N	0.417	neutral	None	None	None	None	I
S/T	0.0602	likely_benign	0.0664	benign	-0.398	Destabilizing	0.001	N	0.131	neutral	None	None	None	None	I
S/V	0.1154	likely_benign	0.1306	benign	-0.404	Destabilizing	None	N	0.281	neutral	None	None	None	None	I
S/W	0.2313	likely_benign	0.2857	benign	-1.168	Destabilizing	0.958	D	0.478	neutral	None	None	None	None	I
S/Y	0.1214	likely_benign	0.1393	benign	-0.86	Destabilizing	0.602	D	0.547	neutral	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.